Treatment of Bacterial Meningitis Caused by Specific Pathogens in Adults

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Treatment of bacterial meningitis caused by specific pathogens in adults
Author: Allan R Tunkel, MD, PhD, MACP

Section Editor: Stephen B Calderwood, MD
Deputy Editor: Jennifer Mitty, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Jun 05, 2017.
INTRODUCTION — Bacterial meningitis is a medical emergency, and immediate steps must be taken to
establish the specific cause and initiate effective therapy. The mortality rate of untreated disease approaches 100
percent and, even with optimal therapy, there is a high failure rate.
The possible presence of bacterial meningitis is suggested by the symptoms of fever, altered mental status,
headache, and nuchal rigidity. Although one or more of these findings are absent in many patients with bacterial
meningitis [1-4], virtually all patients (99 to 100 percent) have at least one of the classic triad of fever, neck
stiffness, and altered mental status [4]. (See "Clinical features and diagnosis of acute bacterial meningitis in
adults".)
The treatment and prevention of bacterial meningitis caused by specific pathogens will be reviewed here. The
epidemiology, pathogenesis, clinical features, diagnosis, initial management, and use of dexamethasone for the
treatment of bacterial meningitis are discussed separately. (See "Epidemiology of bacterial meningitis in adults"
and "Pathogenesis and pathophysiology of bacterial meningitis" and "Clinical features and diagnosis of acute
bacterial meningitis in adults" and "Initial therapy and prognosis of bacterial meningitis in adults" and
"Dexamethasone to prevent neurologic complications of bacterial meningitis in adults".)
APPROACH TO THERAPY — There are a number of general principles of antimicrobial therapy in patients with
bacterial meningitis. The most important initial issues are avoidance of delay in administering therapy and the
choice of drug regimen. (See "Initial therapy and prognosis of bacterial meningitis in adults", section on 'General
principles of therapy'.)
Empiric therapy — Antimicrobial therapy, along with adjunctive dexamethasone when indicated, should be
initiated immediately after the performance of the lumbar puncture (LP) or, if a computed tomography (CT) scan
of the head is to be performed before LP, immediately after blood cultures are obtained. Adjunctive
dexamethasone should be given shortly before or at the same time as the first dose of antimicrobials, when
indicated. (See "Initial therapy and prognosis of bacterial meningitis in adults", section on 'Avoidance of delay'.)
Antimicrobial selection must be empiric immediately after cerebrospinal fluid (CSF) is obtained or when lumbar
puncture is delayed. In such patients, antimicrobial therapy needs to be directed at the most likely bacteria based
upon patient age and underlying comorbid disease (table 1A-B) [3,5].
Empiric therapy is discussed in detail separately. (See "Initial therapy and prognosis of bacterial meningitis in
adults", section on 'Empiric therapy'.)
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Regimens based upon Gram stain — Rather than empiric therapy, intravenous antimicrobial therapy should be
directed at the presumed pathogen if the Gram stain is diagnostic (table 1B-C) [5].
If the CSF findings are consistent with the diagnosis of acute bacterial meningitis but the Gram stain is negative,
empiric antimicrobial therapy should be continued. (See "Initial therapy and prognosis of bacterial meningitis in
adults", section on 'Regimens based upon Gram stain'.)
The antimicrobial regimen should be modified further, when indicated, based on the CSF culture and
susceptibility results.
Route of administration — Because of the general limitation in antimicrobial penetration into the CSF, all
patients should be treated with intravenous antimicrobials. Oral antimicrobials should be avoided since the dose
and tissue concentrations tend to be considerably lower than with parenteral agents.
Adjunctive dexamethasone — Permanent neurologic sequelae, such as hearing loss and focal neurologic
deficits, are not uncommon in survivors of bacterial meningitis, particularly patients with pneumococcal
meningitis. (See "Neurologic complications of bacterial meningitis in adults".)
Early intravenous administration of glucocorticoids (usually dexamethasone) has been evaluated as adjunctive
therapy in an attempt to diminish the rate of hearing loss, other neurologic complications, and mortality. Based
upon clinical trial data from Europe, the main indication for dexamethasone therapy in adults is known or
suspected pneumococcal meningitis. Since the etiology of bacterial meningitis is not usually known at the time of
treatment initiation, dexamethasone is administered to patients in the developed world with suspected bacterial
meningitis in whom the organism is unknown. Dexamethasone should only be continued if the CSF Gram stain
and/or the CSF or blood cultures reveal Streptococcus pneumoniae.
Since the entry of vancomycin into the CSF may be reduced by the decrease in inflammation with
dexamethasone, rifampin is sometimes added in patients receiving dexamethasone. This is discussed in detail
separately. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults", section
on 'Antibiotic regimens'.)
The possible efficacy of dexamethasone therapy in the developing world varies with the patient population.
These issues are discussed in detail elsewhere. (See "Dexamethasone to prevent neurologic complications of
bacterial meningitis in adults".)
THERAPY FOR SPECIFIC PATHOGENS — The prevalence of various pathogens in bacterial meningitis varies
by region of the world. Among adults with bacterial meningitis in the United States, S. pneumoniae and Neisseria
meningitidis are the most common infecting organisms [3,6,7]. (See "Epidemiology of bacterial meningitis in
adults", section on 'Community-acquired meningitis'.)
The following treatment recommendations are in agreement with the 2004 Infectious Diseases Society of
America (IDSA) guidelines for the management of bacterial meningitis and the 2017 IDSA guidelines for
healthcare-associated ventriculitis and meningitis [5,8]. Since there are limited randomized trials regarding the
therapy of specific causes of bacterial meningitis, treatment recommendations are based upon in vitro
susceptibility and pharmacodynamic data as well as accumulated clinical experience.
Directed therapy against a specific organism is recommended when the clinical presentation and results of the
cerebrospinal fluid (CSF) Gram stain are unequivocal (table 1C) or the cultures are already positive (table 1D)
[5,8,9]. If, on the other hand, empiric therapy is begun, the regimen should be adjusted, if necessary, once the
culture results are available (table 1D). For the targeted regimen, agents should have good CNS penetration and
the patient's isolate should demonstrate in vitro susceptibility [8]. Recommended dosages for use in patients with
normal renal and hepatic function are shown in the table (table 1B).
The duration of therapy for meningitis in adults has not been subjected to rigorous trials in the United States or
other developed countries. The recommendations in the following sections reflect general consensus and are
fairly conservative. However, a longer course may be warranted when complicating features are present or the
clinical response is unusually slow. On the other hand, shorter courses (eg, single doses of depot
chloramphenicol or conventional ceftriaxone) have been successful in the management of epidemic
meningococcal meningitis in developing countries. (See "Treatment and prevention of meningococcal infection",
section on 'Empiric treatment during epidemics'.)
Streptococcus pneumoniae — S. pneumoniae is the most common cause of meningitis in adults, particularly in
older adults [3,6]. In a review of 248 patients with bacterial meningitis seen in 1995 in acute care hospitals in 22
counties in 4 states in the United States, S. pneumoniae accounted for 60 percent of cases in adults up to age
60 and almost 70 percent in older patients [6]. In a more recent United States surveillance study between 2003
and 2007 [10], 1083 cases of bacterial meningitis were reported in adults, with S. pneumoniae responsible for 71
percent of cases. (See "Epidemiology of bacterial meningitis in adults", section on 'Community-acquired
meningitis'.)
Although rates of pneumococcal meningitis have been reported to have decreased among both children and
adults since the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in children, there has also
been a concerning increase in meningitis caused by pneumococcal serotypes not in the vaccine (specifically
serotypes 19A, 22F, and 35B). Thus, there is a need for continued monitoring of the serotypes causing invasive
infection. With the licensure of the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 [11], further
declines in the incidence of pneumococcal meningitis may be seen. However, in one study that examined the
impact of PCV13 on the incidence of pneumococcal meningitis in children, the number of cases in 2009
compared with 2007 was unchanged, although the proportion of cases caused by serotypes in the vaccine
decreased significantly [12]. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and
bacteremia", section on 'Impact of childhood vaccination'.)
In the past, the conventional approach to the treatment of pneumococcal meningitis was the administration of
penicillin alone for two weeks at a dose of four million units intravenously (IV) every four hours in patients with
normal renal function. Good results were also obtained with a third-generation cephalosporin, such as
ceftriaxone or cefotaxime [5].
However, the widespread emergence of penicillin-resistant pneumococcus has made penicillin an inappropriate
empiric therapy without proof of in vitro susceptibility. Although many third-generation cephalosporins have good
in vitro activity against strains of pneumococcus that have intermediate susceptibility to penicillin (minimum
inhibitory concentration [MIC] 0.12 to 1.0 mcg/mL) according to the cutoffs used prior to 2008, reports have
raised the possibility of clinical failure when cephalosporin resistance coexists with penicillin resistance (table 2)
[13]. In 2008, the Clinical and Laboratory Standards Institute removed the "intermediate" susceptibility category
(MIC 0.12 to 1 mcg/mL) for the penicillin breakpoints of meningeal isolates of S. pneumoniae, such that all
meningeal isolates with an MIC ≥0.12 are considered resistant. (See "Resistance of Streptococcus pneumoniae
to beta-lactam antibiotics".)
First-line regimens — Initial empiric therapy of S. pneumoniae in patients with normal renal function includes
vancomycin (15 to 20 mg/kg IV every 8 to 12 hours) plus either ceftriaxone (2 g IV every 12 hours) or cefotaxime
(2 g IV every 4 to 6 hours) [5].
In patients with isolates that are susceptible to penicillin (MIC ≤0.06 mcg/mL), penicillin G (4 million units IV every
four hours) can be used instead of a third-generation cephalosporin, although it is also reasonable to continue
therapy with a third-generation cephalosporin given the excellent efficacy, convenient dosing, and affordability of
these agents. If the isolate is resistant to penicillin (MIC ≥0.12 mcg/mL) but is susceptible to third-generation
cephalosporins (MIC <1.0 mcg/mL), ceftriaxone (2 g IV every 12 hours) or cefotaxime (2 g IV every 4 to 6 hours)
are the preferred drugs. Although some retrospective studies have advocated cephalosporin monotherapy for
organisms with MICs up to 1.0 mcg/mL for cefotaxime or ceftriaxone [14,15], it seems more prudent to use the
lower breakpoint (ie, less than 1.0 mcg/mL) [5]. Vancomycin, in combination with a third-generation
cephalosporin, should be continued if there is penicillin resistance (MIC ≥0.12 mcg/mL) and an MIC ≥1.0 mcg/mL
to third-generation cephalosporins (table 1D).
Vancomycin is erratic in its penetration into the CSF and may be ineffective as monotherapy in pneumococcal
meningitis. Nevertheless, it is recommended that vancomycin (15 to 20 mg/kg IV every 8 to 12 hours if renal
function is normal) be given with ceftriaxone or cefotaxime in the initial treatment of pneumococcal meningitis
until susceptibility results are available [5]. The vancomycin dose should not exceed 2 g per dose or a total daily
dose of 60 mg/kg. Serum trough concentrations of vancomycin should range from 15 to 20 mcg/mL. (See
"Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)
As noted above, early intravenous administration of glucocorticoids (usually dexamethasone) has been
evaluated as adjunctive therapy in an attempt to diminish the rate of hearing loss and other neurologic
complications as well as mortality in selected patients with bacterial meningitis. Based upon clinical trial data
from Europe, the main indication for dexamethasone therapy in adults is known or suspected pneumococcal
meningitis. Specific recommendations regarding the use of dexamethasone as adjunctive therapy for bacterial
meningitis are presented separately. (See "Dexamethasone to prevent neurologic complications of bacterial
meningitis in adults".)
In patients receiving adjunctive dexamethasone, the diminished CSF inflammatory response after
dexamethasone administration may reduce CSF vancomycin penetration and delay CSF sterilization. However,
in a study of 14 patients, the administration of intravenous vancomycin (15 mg/kg loading dose, followed by a
continuous infusion of 60 mg/kg per day) led to mean serum and CSF vancomycin concentrations of 25.5 and
7.9 mcg/mL, respectively, indicating that significant CSF concentrations can be attained with appropriate dosing
[16]. If dexamethasone is given, some experts recommend empiric rifampin (600 mg orally or IV once daily) in
addition to vancomycin, since its CSF penetration is unaffected by dexamethasone and it is synergistic with
ceftriaxone against beta-lactam–resistant S. pneumoniae [17]. If susceptibility studies of the isolated
pneumococcus show resistance (MIC >2 mcg/mL) to ceftriaxone and cefotaxime, rifampin may be continued or
added if the organism is susceptible to rifampin [5].
The duration of antimicrobial therapy for pneumococcal meningitis is usually 10 to 14 days.
Alternative agents — Chloramphenicol (1.5 g IV every six hours) has been used in patients with
pneumococcal meningitis who are allergic to penicillin and cephalosporins. However, many penicillin-resistant
strains are also somewhat resistant to chloramphenicol killing (despite in vitro tests that show inhibition), and
treatment failures of meningitis due to penicillin-resistant S. pneumoniae have occurred when chloramphenicol is
used. One series evaluated 25 children with pneumococcal meningitis who had in vitro sensitivity to and were
treated with chloramphenicol; 20 (80 percent) had an unsatisfactory outcome [18].
The older fluoroquinolones have generally lacked sufficient activity against S. pneumoniae to warrant their use in
the therapy of pneumococcal meningitis, but the newer fluoroquinolones, such as moxifloxacin, have shown
excellent in vitro activity and efficacy in animal models of pneumococcal meningitis [19,20]. However, clinical
data are sparse. One fluoroquinolone, trovafloxacin, was compared with ceftriaxone, with or without vancomycin,
in a multicenter randomized trial of 311 children with bacterial meningitis in which 27 percent of cases had
pneumococcal meningitis [21]. The overall efficacy (CSF sterilization and clinical success) of both treatment
groups was similar. Trovafloxacin is no longer utilized because of its association with serious liver toxicity,
although these results suggest the potential usefulness of newer fluoroquinolones in the treatment of bacterial
meningitis.
Although there are not sufficient data to recommend fluoroquinolones as part of the routine treatment of
pneumococcal meningitis, this class is sometimes used in patients with serious allergies to cephalosporins or
vancomycin. If it is not possible to use cephalosporins or vancomycin, moxifloxacin is probably the best choice
as a second agent given its excellent in vitro activity and CSF penetration. For example, in a patient with a
serious cephalosporin allergy, moxifloxacin should be used in combination with vancomycin. Conversely, in a
patient with a serious vancomycin allergy, moxifloxacin should be used in combination with ceftriaxone or
cefotaxime, if the cefotaxime or ceftriaxone MIC is ≥1 mcg/mL. (See "Initial therapy and prognosis of bacterial
meningitis in adults", section on 'Beta-lactam allergy'.)
Neisseria meningitidis — Meningococcal meningitis occurs most commonly in children and young adults.
However, it also accounts for approximately 12 percent of cases of bacterial meningitis in adults [10]. (See
"Epidemiology of bacterial meningitis in adults", section on 'Community-acquired meningitis'.)
Third-generation cephalosporins, such as cefotaxime or ceftriaxone, should be used to treat suspected (eg,
Gram stain with gram-negative diplococci) or culture-proven meningococcal infection prior to susceptibility results
[5]. If the organism is proven to be penicillin susceptible, the treatment can then be switched to penicillin G. The
treatment of meningococcal meningitis is discussed in detail separately. (See "Treatment and prevention of
meningococcal infection", section on 'Treatment'.)
A seven-day duration of therapy is adequate for meningococcal meningitis. However, there may still be
nasopharyngeal colonization with the infecting strain. As a result, the index patient may need to take an agent
that eradicates colonization (eg, rifampin or ciprofloxacin) to avoid transmission to others. This is discussed in
detail separately. (See "Treatment and prevention of meningococcal infection", section on 'Antimicrobial
chemoprophylaxis'.)
Droplet precautions should be used for 24 hours after starting effective antimicrobial therapy in patients with
suspected or confirmed N. meningitidis infection [22]. (See "Infection prevention: Precautions for preventing
transmission of infection", section on 'Droplet precautions'.)
Haemophilus influenzae — Haemophilus influenzae type b meningitis has decreased markedly in children
following widespread vaccination of infants. However, strains other than type b continue to cause occasional
invasive infection (including meningitis) in children and adults. In the review cited above of bacterial meningitis in
the United States in 1995, H. influenzae accounted for 7 percent of cases in adults. Only 10 percent of adult H.
influenzae meningitis cases were caused by serotype b strains; the remainder were caused by types a, e, and f
[6]. In a more recent surveillance study, H. influenzae accounted for 6 percent of cases in adults; a majority of the
strains (almost 75 percent) were not able to be serotyped [10].
The evolution of treatment recommendations for H. influenzae type b infection has paralleled changes in this
organism's susceptibility profile. The results of numerous clinical trials have shown that third-generation
cephalosporins, such as cefotaxime or ceftriaxone, are as effective for ampicillin-resistant as for ampicillin-
susceptible organisms.
A third-generation cephalosporin (either cefotaxime or ceftriaxone) is the drug of choice for H. influenzae
meningitis. The best data supporting this recommendation come from randomized trials in children. One such
trial compared ceftriaxone with cefuroxime (a second-generation cephalosporin with good CSF penetration) in
children with bacterial meningitis, which was due to H. influenzae in the majority of cases [23]. Ceftriaxone was
significantly more likely to sterilize the CSF at 24 hours (100 versus 90 percent) and was associated with a lesser
likelihood of hearing impairment at the conclusion of therapy (11 versus 18 percent). Virtually identical findings
were noted in a second randomized trial comparing these two drugs [24]. If the organism does not produce beta-
lactamase, ampicillin is also an effective therapy.
We recommend a regimen of ceftriaxone (2 g IV twice daily) or cefotaxime (2 g IV every four to six hours) in
adults; therapy should be continued for at least seven days.
Pharyngeal colonization persists after curative therapy and may require a short course of rifampin if there are
children in the household at risk for invasive Haemophilus infection. This is a rare situation because conjugate
vaccines for H. influenzae type b are widely used and highly effective. (See 'Chemoprophylaxis' below.)
Listeria monocytogenes — Listeria, a gram-positive bacillus, is an important cause of bacteremia and

meningitis, particularly in older adults (in whom it accounts for approximately 20 percent of cases [6]), pregnant
women [25], and patients with impaired cell-mediated immunity [26]. When Listeria invades the bloodstream, it
has a tropism for the central nervous system (CNS) [27]. It is more likely than other causes of meningitis to
cause small brain abscesses, especially in the midbrain and brainstem [28]. These lesions can account for many
of the long-term sequelae of listerial meningitis. (See "Clinical manifestations and diagnosis of Listeria
monocytogenes infection".)
Drugs of choice — Listeria has traditionally been treated with ampicillin (2 g every four hours) or penicillin G
(4 million units every four hours), since resistance to these drugs is rare [29]. Gentamicin is added for synergy,
despite its poor penetration into the CSF [30]. The gentamicin dose (5 mg/kg per day in a person with normal
renal function) is divided into three equal doses. Gentamicin has not been studied as a synergistic drug with any
therapy other than the penicillin or ampicillin.
Ampicillin is given for at least 21 days in patients with Listeria meningitis; gentamicin is given until the patient
improves (for at least the first week) or, in poor responders, for up to three weeks if there are no signs of
nephrotoxicity or ototoxicity. Patients with cerebritis or rhombencephalitis should be treated for at least six weeks.
(See "Treatment, prognosis, and prevention of Listeria monocytogenes infection".)
Alternative regimens — If a penicillin- or cephalosporin-allergic patient cannot be desensitized and receive a

beta-lactam antimicrobial, an alternative therapy is trimethoprim-sulfamethoxazole (TMP-SMX; 5 mg/kg [based
on the trimethoprim component] IV every 6 to 12 hours) [5,31]. In one retrospective series, therapy with TMP-
SMX plus ampicillin correlated with a lower failure rate and fewer neurologic sequelae than ampicillin combined
with an aminoglycoside [32], although the results of this small study are not compelling enough to make a
change in recommended therapy [29].
Imipenem and meropenem have excellent in vitro activity against Listeria. Meropenem has been used to
successfully treat some patients with Listeria meningitis, although more data are needed. Some newer
fluoroquinolones and linezolid show good in vitro activity against Listeria, but clinical experience is mixed. (See
"Treatment, prognosis, and prevention of Listeria monocytogenes infection", section on 'Alternative drugs'.)
Gram-negative bacilli — Aerobic gram-negative bacilli, such as Escherichia coli and Klebsiella species, are rare
causes of community-acquired meningitis in adults but are a common cause of healthcare-associated infections,
mostly following neurosurgical procedures [8,33]. In a review of 493 episodes of bacterial meningitis in the
Boston area from 1962 to 1988, gram-negative bacilli accounted for 3 percent of community-acquired cases and
33 percent of nosocomial cases [3].
Treatment of infection caused by gram-negative bacilli should be based upon in vitro susceptibility testing, and
agents used should have good CNS penetration [8]. For patients with meningitis caused by gram-negative bacilli
susceptible to third-generation cephalosporins (ceftriaxone, cefotaxime) such as Enterobacteriaceae, one of
these agents should be used [8]. However, given the emergence of strains of gram-negative bacilli that are
resistant to the third-generation cephalosporins [34], other agents (given intravenously, with or without
intraventricular therapy) may need to be given. The approach to such infections is discussed below. (See
'Resistant gram-negative bacilli' below.)
Because of the difficulty in curing meningitis caused by gram-negative bacilli, a repeat CSF sample should be
considered for culture two to three days into therapy to help assess the efficacy of treatment. (See "Initial therapy
and prognosis of bacterial meningitis in adults", section on 'Repeat CSF analysis'.)
The duration of therapy should be at least 21 days.
Resistant gram-negative bacilli — Gram-negative bacilli such as Pseudomonas aeruginosa and

Acinetobacter spp are often resistant to many commonly used antimicrobials. For Pseudomonas spp, the
recommended agents include ceftazidime, cefepime, or meropenem [8]. Alternative agents are aztreonam or a
fluoroquinolone with in vitro activity.
Ceftazidime (2 g IV every eight hours) has been the most consistently effective cephalosporin for P. aeruginosa
infections, including meningitis [35]. Cefepime, which has a similar gram-negative spectrum as ceftazidime, has
also shown efficacy in isolated case reports [36].
Carbapenems such as meropenem should be used in patients with meningitis caused by ceftazidime-resistant
strains of various gram-negative bacilli, such as Acinetobacter spp and extended-spectrum beta-lactamase–
producing organisms [8]. Meropenem has been found to be an effective drug in the treatment of meningitis [37],
and it may have a lower epileptogenic potential than imipenem [38]. Prolonged infusions of meropenem (each
dose administered over three hours) may be beneficial for treating resistant gram-negative bacilli, although this
has not been studied in detail in patients with meningitis [8,39]. Imipenem should be used with caution since it
has been associated with seizures when doses exceeding 2 g/day are given to patients with impaired renal
function [40].
The treatment of gram-negative meningitis caused by isolates that are resistant to ceftazidime, cefepime, and the
carbapenems is challenging due to the toxicity of alternative agents and/or limited data on their use [33].
Intravenous colistin (usually formulated as colistimethate sodium) is an alternative agent for Acinetobacter
meningitis, but its use is limited by the potential for severe nephrotoxicity. In difficult-to-eradicate infections,
colistin can also be administered by the intraventricular or intrathecal route [41-43]. Fluoroquinolones (eg,
ciprofloxacin and moxifloxacin) have been used in some patients with gram-negative meningitis, but there are
only limited data about their efficacy [19,44]. Options for the treatment of meningitis caused by resistant gram-
negative bacilli are presented in detail separately. (See "Gram-negative bacillary meningitis: Treatment" and
"Acinetobacter infection: Treatment and prevention".)
The usual duration of therapy should be at least 21 days.
Staphylococcus aureus — Staphylococcus aureus meningitis is typically associated with penetrating head
trauma or neurosurgery [5]. Given substantial rates of methicillin-resistant S. aureus (MRSA), vancomycin (15 to
20 mg/kg IV every 8 to 12 hours if renal function is normal) should be used as initial therapy when S. aureus is
suspected or proven (table 1A and table 1B) [5,45]. The vancomycin dose should not exceed 2 g per dose or a
total daily dose of 60 mg/kg. If susceptibility testing reveals methicillin-susceptible S. aureus (MSSA), therapy
should be changed to nafcillin (2 g IV every four hours) or oxacillin (2 g IV every four hours). Cefazolin should
not be used for MSSA meningitis because it does not adequately penetrate into the CNS. If the organism is
methicillin resistant, vancomycin should be continued and dosed to achieve serum trough concentrations of 15 to
20 mcg/mL. (See "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)
A significant drawback to vancomycin is its poor penetration into the CSF of approximately 1 and 5 percent with
uninflamed and inflamed meninges, respectively [45-48]. Rifampin can be added to vancomycin at a dose of 600
mg orally or IV once daily or 300 to 450 mg twice daily because it achieves bactericidal concentrations in the
cerebrospinal fluid regardless of meningeal inflammation [5,45,49], although there are few data to support this
[50-52].
Although there are insufficient data regarding the efficacy of alternative agents for the treatment of meningitis
caused by MRSA, linezolid, daptomycin (usually combined with rifampin), and trimethoprim-sulfamethoxazole
are reasonable options when vancomycin cannot be used or is ineffective. If the patient's MRSA isolate has a
vancomycin minimum inhibitory concentration ≥1 mcg/mL and the patient has not had an appropriate clinical or
microbiologic response, one of the alternative regimens can be used [8]. Linezolid has good CSF penetration of
approximately 66 percent [45,53-55], and TMP-SMX has moderately good CSF penetration (13 to 53 percent for
TMP and 17 to 63 percent for SMX) [45,56,57]. In a rabbit meningitis model, CSF daptomycin penetration was 5
to 6 percent and achieved adequate concentrations [45,58,59]. Based upon case reports and case series of
patients with CNS infections caused by MRSA, alternatives to vancomycin include linezolid (600 mg IV twice
daily) [60-63], TMP-SMX (5 mg/kg of the trimethoprim component IV every 8 to 12 hours) [45,56,64], and
daptomycin (6 to 10 mg/kg IV once daily) usually combined with rifampin [65,66]. Further studies are needed to
establish the benefit of these agents for the treatment of meningitis.
The duration of therapy for S. aureus meningitis is at least 14 days [45].
REGIMENS IN PATIENTS WITH DRUG ALLERGIES — The approach to therapy in patients with antimicrobial
allergies is challenging, given the importance of early initiation of therapy and the role of beta-lactam
antimicrobial regimens in the therapy of bacterial meningitis. Although it is optimal to desensitize patients with a
history of anaphylaxis to beta-lactams who require therapy with this antimicrobial class, an alternative regimen
must be used while the desensitization is being performed. Furthermore, the decision of whether a beta-lactam is
a necessary part of the regimen is based on the Gram stain and/or culture data, the latter of which can take
several days to yield an organism.
For some bacteria, regimens that do not include a beta-lactam are sufficient but, for others, a beta-lactam is the
optimal therapy. (See 'Alternative agents' above and 'Listeria monocytogenes' above and "Initial therapy and
prognosis of bacterial meningitis in adults", section on 'Beta-lactam allergy'.)
OUTPATIENT THERAPY — Outpatient antimicrobial therapy may be appropriate for selected patients with
bacterial meningitis because, when complications occur, they usually happen within the first two to three days of
therapy. Treatment outside of the hospital leads to decreased costs of hospitalization, decreased risk of
development of nosocomial infections, and improved quality of life. Patients who are candidates for outpatient
therapy should continue to receive intravenous antimicrobials for the entire course. (See 'Route of administration'
above.)
The following criteria have been suggested as a guide for outpatient antimicrobial therapy in patients with
bacterial meningitis [5,67,68]:
● Inpatient therapy for >6 days
● Absence of fever for at least 24 to 48 hours prior to initiation of outpatient therapy
● No significant neurologic dysfunction, focal findings, or seizure activity
● Clinical stability or improving infection
● Ability to take fluids by mouth
● Access to home health nursing for antimicrobial administration
● Reliable intravenous line and infusion device (if needed)
● Daily availability of a physician
● Established plan for physician visits, nurse visits, laboratory monitoring, and emergencies
● Patient and/or family compliance
● Safe environment with access to a telephone, utilities, food, and refrigerator
PREVENTION — Some forms of bacterial meningitis can be prevented by successful vaccination, and temporary
protection can be provided in certain cases with chemoprophylaxis.
Vaccines — Among the major causes of bacterial meningitis in adults, vaccines are available for S. pneumoniae,
N. meningitidis, and H. influenzae. Vaccines against S. pneumoniae and N. meningitidis are recommended for
adults with a variety of risk factors for infection. Routine immunization of adults against H. influenzae type b is not
recommended, except for those with prior splenectomy. The indications for vaccination are discussed separately.
(See "Pneumococcal vaccination in adults" and "Meningococcal vaccines" and "Prevention of sepsis in the
asplenic patient", section on 'Haemophilus influenzae vaccine'.)
Chemoprophylaxis
Specific organisms — There is a role for postexposure chemoprophylaxis to prevent spread of

meningococcal and Haemophilus meningitis under certain circumstances but not for pneumococcal disease.
Indications for chemoprophylaxis are discussed in detail separately. (See "Treatment and prevention of
meningococcal infection", section on 'Antimicrobial chemoprophylaxis' and "Prevention of Haemophilus
influenzae type b infection", section on 'Postexposure chemoprophylaxis'.)
Basilar skull fracture and cerebrospinal fluid leak — Basilar skull fractures with underlying dural tears are
associated with cerebrospinal fluid (CSF) leaks and predispose patients to meningitis because of the potential for
direct communication of bacteria in the upper respiratory tract with the central nervous system. However, most
CSF leaks resolve spontaneously within one week of injury and without complications; in addition, most CSF
leaks following trauma are not recognized [8,33]. We recommend against using prophylactic antimicrobials in
those with a basilar skull fracture and CSF leak because there is no evidence of benefit [8]. A meta-analysis of
five randomized trials and 17 other studies (involving over 2000 patients) of antibiotic prophylaxis following
basilar skull fracture concluded that routine prophylaxis is not supported by the available evidence but noted that
this evidence contains methodological shortcomings and is therefore not conclusive [69].
Among patients with a basilar skull fracture and a CSF leak who develop meningitis, the median time between
the injury and the onset of meningitis is 11 days [33,70,71]. In patients with a basilar skull fracture and a
prolonged CSF leak (>7 days), an attempt should therefore be made to repair the leak [8]. (See "Skull fractures
in adults", section on 'Basilar skull fracture'.)
Patients with a CSF leak (due to either basilar skull fracture or another cause) should receive both the
pneumococcal conjugate vaccine and the pneumococcal polysaccharide vaccine [8]. The schedule for
administration of these vaccines is summarized in the following algorithm and discussed in detail separately
(algorithm 1). (See "Pneumococcal vaccination in adults", section on 'PCV13 and PPSV23' and "Pneumococcal
vaccination in adults", section on 'Schedule for dual vaccination'.)
Neurosurgery — Perioperative antimicrobial prophylaxis is indicated for patients undergoing neurosurgery,

including procedures to place CSF shunts or other hardware [8]. (See "Antimicrobial prophylaxis for prevention of
surgical site infection in adults", section on 'Neurosurgery' and "Infections of cerebrospinal fluid shunts and other
devices", section on 'Antibiotic prophylaxis'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries
and regions around the world are provided separately. (See "Society guideline links: Bacterial meningitis in
adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
"patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Bacterial meningitis (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Among adults with bacterial meningitis in the United States, Streptococcus pneumoniae and Neisseria
meningitidis are the most common infecting organisms. (See 'Introduction' above.)
Treatment approach
● Antimicrobial selection must be empiric immediately after cerebrospinal fluid (CSF) is obtained or when
lumbar puncture (LP) is delayed. In such patients, antimicrobial therapy needs to be directed at the most
likely bacteria based upon patient age and underlying comorbid disease (table 1A-B). (See 'Empiric therapy'
above.)
● We recommend that antimicrobial therapy be initiated immediately after the performance of the LP or, if a
computed tomography (CT) scan of the head is to be performed before LP, immediately after blood cultures
are obtained (Grade 1B). Adjunctive dexamethasone should be given shortly before or at the same time as
the first dose of antimicrobials, when indicated. (See "Initial therapy and prognosis of bacterial meningitis in
adults", section on 'Empiric therapy'.)
● For adults in the developed world with suspected bacterial meningitis in whom the organism is unknown or
Streptococcus pneumoniae is confirmed, we recommend administration of dexamethasone (Grade 1B).
Dexamethasone should be continued if the CSF Gram stain and/or the CSF or blood cultures reveal S.
pneumoniae. The indications for dexamethasone in patients in the developing world with suspected or
confirmed bacterial meningitis are less certain and are discussed in detail elsewhere. Rifampin is added to
the regimen in patients receiving dexamethasone under certain circumstances. (See "Dexamethasone to
prevent neurologic complications of bacterial meningitis in adults".)
● Rather than empiric therapy, antimicrobials should be directed at the presumed pathogen if the Gram stain is
diagnostic (table 1B-C). (See 'Regimens based upon Gram stain' above.)
● The antimicrobial regimen should be modified further, when indicated, based on the CSF culture and
susceptibility results (table 1B, 1D). (See 'Therapy for specific pathogens' above.)
● Because of the general limitation in antimicrobial penetration into the CSF, all patients should be treated with
intravenous (IV) antimicrobials. (See 'Route of administration' above.)
Pathogen-directed therapy
● For the initial therapy of S. pneumoniae, we recommend vancomycin plus either ceftriaxone or cefotaxime
rather than a third-generation cephalosporin alone (Grade 1B). (See 'First-line regimens' above.)
• If the isolate is proven to be susceptible to penicillin (minimum inhibitory concentration [MIC] ≤0.06
mcg/mL), monotherapy with penicillin G or ampicillin can be used. It is also reasonable to continue
therapy with a third-generation cephalosporin alone instead of changing to penicillin or ampicillin, given
the excellent efficacy, convenient dosing, and affordability of these agents.
• If the isolate is resistant to penicillin (MIC ≥0.12 mcg/mL), but susceptible to third-generation
cephalosporins (MIC <1.0 mcg/mL), either cefotaxime or ceftriaxone should be used. However, if the
isolate is resistant to both penicillin and third-generation cephalosporins, vancomycin plus a third-
generation cephalosporin should be continued for the total duration of therapy (table 1B, 1D).
• The dosing for patients with normal renal function is:
- Vancomycin – 15 to 20 mg/kg IV every 8 to 12 hours (not to exceed 2 g per dose or a total daily
dose of 60 mg/kg; adjust dose to achieve vancomycin serum trough concentrations of 15 to 20
mcg/mL)
- Ceftriaxone – 2 g IV every 12 hours
- Cefotaxime – 2 g IV every four to 6 hours
- Penicillin G – 4 million units IV every 4 hours
- Ampicillin – 2 g IV every 4 hours
● For the initial therapy of N. meningitidis, we recommend a third-generation cephalosporin, such as

cefotaxime or ceftriaxone, rather than penicillin, while awaiting susceptibility data (table 1B-C) (Grade 1C). If
the isolate is susceptible to penicillin, either a third-generation cephalosporin or penicillin may be used to
complete the course of therapy (table 1B, 1D). (See 'Neisseria meningitidis' above.)
● The preferred regimens for other causes of bacterial meningitis are discussed above (table 1B-C and table
1B, 1D). (See 'Haemophilus influenzae' above and 'Listeria monocytogenes' above and 'Gram-negative
bacilli' above and 'Staphylococcus aureus' above.)
● The optimal regimens for patients with severe drug allergies depends upon the organism. (See 'Alternative
agents' above and 'Listeria monocytogenes' above and "Initial therapy and prognosis of bacterial meningitis
in adults", section on 'Beta-lactam allergy'.)
Prevention
● Vaccines against N. meningitidis and S. pneumoniae are recommended for adults at increased risk of these
infections. (See 'Vaccines' above.)
● There is a role for postexposure chemoprophylaxis to prevent spread of meningococcal and Haemophilus
meningitis under certain circumstances. (See 'Chemoprophylaxis' above.)
● For patients with a basilar skull fracture and a CSF leak, we recommend against using prophylactic
antimicrobials (Grade 1B). If the CSF leak persists for >7 days, an attempt should be made to repair it.
Patients with a CSF leak (due to either basilar skull fracture or another cause) should receive both the
pneumococcal conjugate vaccine and the pneumococcal polysaccharide vaccine; the schedule for
vaccination is summarized in the following algorithm (algorithm 1). (See 'Basilar skull fracture and
cerebrospinal fluid leak' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
Topic 1283 Version 29.0
GRAPHICS
Recommendations for empiric antimicrobial therapy for purulent meningitis based

on patient age and specific predisposing condition*
Predisposing
Common bacterial pathogens Antimicrobial therapy
factor
Age
<1 month Streptococcus agalactiae, Escherichia coli, Ampicillin plus cefotaxime; OR ampicillin plus
Listeria monocytogenes an aminoglycoside
1 to 23 months Streptococcus pneumoniae, Neisseria Vancomycin plus a third-generation

meningitidis, S. agalactiae, Haemophilus cephalosporin ¶ Δ ◊
influenzae, E. coli
2 to 50 years N. meningitidis, S. pneumoniae Vancomycin plus a third-generation

cephalosporin ¶ Δ ◊
>50 years S. pneumoniae, N. meningitidis, L. Vancomycin plus ampicillin plus a third-

monocytogenes, aerobic gram-negative generation cephalosporin ¶ Δ
bacilli
Head trauma
Basilar skull fracture S. pneumoniae, H. influenzae, group A beta- Vancomycin plus a third-generation
hemolytic streptococci cephalosporin ¶ Δ
Penetrating trauma Staphylococcus aureus, coagulase-negative Vancomycin plus cefepime; OR vancomycin

staphylococci (especially Staphylococcus plus ceftazidime; OR vancomycin plus
epidermidis), aerobic gram-negative bacilli meropenem
(including Pseudomonas aeruginosa)
Postneurosurgery Aerobic gram-negative bacilli (including P. Vancomycin plus cefepime; OR vancomycin

aeruginosa), S. aureus, coagulase-negative plus ceftazidime; OR vancomycin plus
staphylococci (especially S. epidermidis) meropenem
Immunocompromised S. pneumoniae, N. meningitidis, L. Vancomycin plus ampicillin plus cefepime; OR

state monocytogenes, aerobic gram-negative vancomycin plus ampicillin plus meropenem
bacilli (including P. aeruginosa)
* For recommended dosages for adults, refer to the UpToDate table on recommended intravenous dosages of antimicrobial
therapy for adults with bacterial meningitis.
¶ Ceftriaxone or cefotaxime.
Δ Some experts would add rifampin if dexamethasone is also given.
◊ Add ampicillin if meningitis caused by Listeria monocytogenes is suspected.
Modified with permission from: Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial
meningitis. Clin Infect Dis 2004; 39:1267. Copyright © 2004 University of Chicago Press.
Graphic 71968 Version 5.0
Recommended intravenous dosages of antimicrobial therapy for adults with

bacterial meningitis who have normal renal and hepatic function
Antimicrobial agent Dose (adult)
Amikacin 5 mg/kg every 8 hours*
Ampicillin 2 g every 4 hours
Aztreonam 2 g every 6 to 8 hours
Cefepime 2 g every 8 hours
Cefotaxime 2 g every 4 to 6 hours
Ceftazidime 2 g every 8 hours
Ceftriaxone 2 g every 12 hours
Chloramphenicol 1 to 1.5 g every 6 hours ¶
Ciprofloxacin 400 mg every 8 to 12 hours
Gentamicin 1.7 mg/kg every 8 hours*
Meropenem 2 g every 8 hours
Moxifloxacin 400 mg every 24 hours Δ
Nafcillin 2 g IV every 4 hours
Oxacillin 2 g IV every 4 hours
Penicillin G potassium 4 million units every 4 hours
Rifampin 600 mg every 24 hours ◊
Tobramycin 1.7 mg/kg every 8 hours*
Trimethoprim-sulfamethoxazole (cotrimoxazole) 5 mg/kg every 6 to 12 hours § ¥
Vancomycin 15 to 20 mg/kg every 8 to 12 hours ‡
IV: intravenously; MRSA: methicillin-resistant Staphylococcus aureus.

* Dose based on ideal body weight or dosing weight except in underweight patients. A calculator for ideal body weight and
dosing weight is available in UpToDate. Dosage and interval must be individualized to produce a peak serum concentration of
7 to 9 mg/L and trough <1 to 2 mg/L for gentamicin or tobramycin and a peak of 25 to 40 mg/L and trough <4 to 8 mg/L for
amikacin. For additional information, refer to the UpToDate topic on aminoglycosides.
¶ The higher dose is recommended for patients with pneumococcal meningitis.
Δ No data on optimal dosage needed in patients with bacterial meningitis.
◊ For the treatment of MRSA meningitis, the Infectious Diseases Society of America (IDSA) suggests a rifampin dose of 600
mg orally once daily or 300 to 450 mg twice daily. [1]
§ Dosage is based on the trimethoprim component.
¥ For the treatment of MRSA meningitis, the IDSA suggests a trimethoprim-sulfamethoxazole dose of 5 mg/kg (based on the
trimethoprim component) intravenously twice or three times daily. [1]
‡ The vancomycin dose should not exceed 2 g per dose or a total daily dose of 60 mg/kg. Adjust dose to achieve vancomycin
serum trough concentrations of 15 to 20 mcg/mL. [1]
Reference:
1. Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the
Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children: Executive Summary. Clin
Infect Dis 2011; 52:285.
Recommendations for antimicrobial therapy of bacterial meningitis in adults with

presumptive pathogen identification by positive Gram stain*
Microorganism Recommended therapy Alternative therapies
Streptococcus pneumoniae Vancomycin plus a third-generation Fluoroquinolone ◊

cephalosporin ¶ Δ
Neisseria meningitidis Third-generation cephalosporin ¶ Chloramphenicol, fluoroquinolone,

aztreonam
Listeria monocytogenes Ampicillin § or penicillin G § Trimethoprim-sulfamethoxazole
Haemophilus influenzae Third-generation cephalosporin ¶ Chloramphenicol, cefepime,

meropenem, fluoroquinolone
* For recommended dosages, refer to the UpToDate table on recommended intravenous dosages of antimicrobial therapy for
adults with bacterial meningitis.
¶ Ceftriaxone or cefotaxime.
Δ Some experts would add rifampin if dexamethasone is also given.
◊ Moxifloxacin is recommended given its excellent cerebrospinal fluid penetration and in vitro activity against Streptococcus
pneumoniae, although there are no clinical data available. If used, many authorities would combine moxifloxacin with
vancomycin or a third-generation cephalosporin (cefotaxime or ceftriaxone).
§ Addition of an aminoglycoside should be considered.
http://www.journals.uchicago.edu/
Recommendations for specific antimicrobial therapy of bacterial meningitis based

on isolated pathogen and susceptibility testing*
Microorganism,
Standard therapy Alternative therapies ¶
susceptibility
Streptococcus pneumoniae
Penicillin MIC
≤0.06 mcg/mL Penicillin G or ampicillin Third-generation cephalosporin Δ,
chloramphenicol
≥0.12 mcg/mL
Third-generation cephalosporin Δ Third-generation cephalosporin Δ Cefepime, meropenem
MIC <1 mcg/mL
Third-generation cephalosporin Δ Vancomycin plus a third-generation Fluoroquinolone §
MIC ≥1 mcg/mL cephalosporin Δ ◊
Neisseria meningitidis
Penicillin MIC
<0.1 mcg/mL Penicillin G or ampicillin Third-generation cephalosporin Δ,
chloramphenicol
0.1 to 1.0 mcg/mL Third-generation cephalosporin Δ Fluoroquinolone, meropenem,
chloramphenicol
Listeria monocytogenes Ampicillin ¥ or penicillin G ¥ Trimethoprim-sulfamethoxazole
Streptococcus agalactiae (group B Ampicillin ¥ or penicillin G ¥ Third-generation cephalosporin Δ

Streptococcus)
Escherichia coli and other Third-generation cephalosporin Δ Aztreonam, fluoroquinolone,

Enterobacteriaceae ‡ meropenem, trimethoprim-
sulfamethoxazole, ampicillin
Pseudomonas aeruginosa ‡ Cefepime or ceftazidime Aztreonam, ciprofloxacin, meropenem
Acinetobacter baumannii Meropenem Colistin (usually formulated as

colistimethate sodium) † or polymyxin
B†
Haemophilus influenzae
Beta-lactamase negative Ampicillin Third-generation cephalosporin Δ,
cefepime, fluoroquinolone, aztreonam,
chloramphenicol
Beta-lactamase positive Third-generation cephalosporin Δ Cefepime, fluoroquinolone, aztreonam,
chloramphenicol
Staphylococcus aureus
Methicillin susceptible Nafcillin or oxacillin Vancomycin, meropenem, linezolid,
daptomycin
Methicillin resistant Vancomycin** Trimethoprim-sulfamethoxazole, linezolid,
daptomycin
Staphylococcus epidermidis Vancomycin** Linezolid
Enterococcus species
Ampicillin susceptible Ampicillin plus gentamicin ...
Ampicillin resistant Vancomycin plus gentamicin ...
Ampicillin and vancomycin resistant Linezolid ...
MIC: minimum inhibitory concentration.

* For recommended dosages, refer to the UpToDate table on the recommended intravenous doses of antimicrobial therapy for
adults with bacterial meningitis.
¶ There may not be clinical data to support all recommendations for alternative antibiotics in patients with bacterial
meningitis, but specific agents are recommended based on cerebrospinal fluid (CSF) penetration in experimental animal
models and in vitro activity against the offending organism.

Δ Ceftriaxone or cefotaxime.
◊ Consider addition of rifampin if the MIC of ceftriaxone is >2 mcg/mL.
§ Moxifloxacin is recommended given its excellent CSF penetration and in vitro activity against Streptococcus pneumoniae,
although there are no clinical data available. If used, many authorities would combine moxifloxacin with vancomycin or a
third-generation cephalosporin (cefotaxime or ceftriaxone).
¥ Addition of an aminoglycoside should be considered.
‡ Choice of a specific antimicrobial regimen must be guided by in vitro susceptibility test results.
† Should be administered not only by the intravenous route but also by the intraventricular or intrathecal route.
** Consider addition of rifampin.
Reference:
1. van de Beek D, Brouwer MC, Thwaites GE, Tunkel AR. Advances in the treatment of bacterial meningitis. Lancet 2012;
380:1693.
http://www.journals.uchicago.edu/
Interpretive breakpoints for Streptococcus pneumoniae for selected antibiotics
Antibiotic Susceptible Intermediate Resistant
Penicillin G (parenteral)
Meningitis ≤0.06 mcg/mL – ≥0.12 mcg/mL
Non-meningitis* ≤2 mcg/mL 4 mcg/mL ≥8 mcg/mL
Penicillin V (oral)* ≤0.06 mcg/mL 0.12 to 1 mcg/mL ≥2 mcg/mL
Amoxicillin (non-meningitis) ≤2 mcg/mL 4 mcg/mL ≥8 mcg/mL
Cefuroxime
Parenteral ≤0.5 mcg/mL 1 mcg/mL ≥2 mcg/mL
Oral ≤1 mcg/mL 2 mcg/mL ≥4 mcg/mL
Cefotaxime, Ceftriaxone
Meningitis ≤0.5 mcg/mL 1 mcg/mL ≥2 mcg/mL
Non-meningitis ≤1 mcg/mL 2 mcg/mL ≥4 mcg/mL
Cefpodoxime ≤0.5 mcg/mL 1 mcg/mL ≥2 mcg/mL
Cefdinir ≤0.5 mcg/mL 1 mcg/mL ≥2 mcg/mL
Clindamycin ≤0.25 mcg/mL 0.5 mcg/mL ≥1 mcg/mL
Rifampin ≤1 mcg/mL 2 mcg/mL ≥4 mcg/mL
Azithromycin ≤0.5 mcg/mL 1 mcg/mL ≥2 mcg/mL
Clarithromycin ≤0.25 mcg/mL 0.5 mcg/mL ≥2 mcg/mL
Gemifloxacin ≤0.12 mcg/mL 0.25 mcg/mL ≥0.5 mcg/mL
Levofloxacin ≤2 mcg/mL 4 mcg/mL ≥8 mcg/mL
Moxifloxacin ≤1 mcg/mL 2 mcg/mL ≥4 mcg/mL
When the E-test is used to determine minimum inhibitory concentrations (MICs), exact results are reported rather
than the twofold dilutions that were used when the cut-offs were defined. An MIC value that falls between standard
twofold dilutions must therefore be rounded up to the next dilution in order to be categorized. As an example, an S.
pneumoniae isolate from a patient with meningitis with a cefotaxime/ceftriaxone MIC of 1.5 mcg/mL would be
rounded up to 2 mcg/mL and would be considered resistant.
* For non-meningitis isolates, the penicillin MIC can predict susceptibility to other beta-lactams as follows:
Penicillin MICs ≤0.06 mcg/mL indicate susceptibility to ampicillin (oral or parenteral), ampicillin-sulbactam, cefaclor,
cefdinir, cefditoren, cefpodoxime, cefprozil, ceftizoxime, cefuroxime, imipenem, loracarbef, and meropenem.
Penicillin MICs ≤2 mcg/mL indicate susceptibility to amoxicillin, amoxicillin-clavulanate, cefepime, cefotaxime,
ceftriaxone, and ertapenem.
Data from: Clinical Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing;
Nineteenth Informational Supplement. CLSI document M100-S19. Clinical and Laboratory Standards Institute, 940 West
Valley Road, Suite 1400, Wayne, PA 19087, USA, 2009.
UpToDate recommendations* for pneumococcal

vaccination in adults (≥19 years of age) with a cochlear
implant, CSF leak, or history of invasive pneumococcal
disease ¶Δ in the United States
CSF: cerebrospinal fluid; PCV13: 13-valent pneumococcal conjugate vaccine (Prevnar

13); PPSV23: 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23).
* UpToDate's recommendations differ from those of the United States Advisory
Committee on Immunization Practices (ACIP). Refer to the UpToDate topic on
pneumococcal vaccination in adults for additional information.
¶ This algorithm applies only to immunocompetent patients who have a cochlear
implant, CSF leak, or history of invasive pneumococcal disease. Refer to the relevant
UpToDate topics for recommendations regarding other patient groups.
Δ UpToDate recommends PCV13 and PPSV23 for patients with a history of invasive
pneumococcal disease as outlined in this algorithm. In contrast, the ACIP has not
issued a recommendation about pneumococcal vaccination of such patients.
◊ Only a single dose of PCV13 is indicated during adulthood.
§ The ACIP recommends a dose of PPSV23 at or after 65 years of age but does not
recommend additional doses of PPSV23 every 10 years thereafter; in contrast,
UpToDate recommends such revaccination.
Reference: Centers for Disease Control and Prevention (CDC). Use of 13-valent
pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine
for adults with immunocompromising conditions: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012;
61:816.

Treatment of Bacterial Meningitis Caused by Specific Pathogens in Adults

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Treatment of Bacterial Meningitis Caused by Specific Pathogens in Adults

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4/3/2018 Treatment of bacterial meningitis caused by specific pathogens in adults - UpToDate

Official reprint from UpToDate®

Treatment of bacterial meningitis caused by specific pathogens in adults

Author: Allan R Tunkel, MD, PhD, MACP

The duration of antimicrobial therapy for pneumococcal meningitis is usually 10 to 14 days.

Listeria monocytogenes — Listeria, a gram-positive bacillus, is an important cause of bacteremia and

Alternative regimens — If a penicillin- or cephalosporin-allergic patient cannot be desensitized and receive a

The duration of therapy should be at least 21 days.

Resistant gram-negative bacilli — Gram-negative bacilli such as Pseudomonas aeruginosa and

The usual duration of therapy should be at least 21 days.

The duration of therapy for S. aureus meningitis is at least 14 days [45].

● Inpatient therapy for >6 days

● Absence of fever for at least 24 to 48 hours prior to initiation of outpatient therapy

● No significant neurologic dysfunction, focal findings, or seizure activity

● Clinical stability or improving infection

● Ability to take fluids by mouth

● Access to home health nursing for antimicrobial administration

● Reliable intravenous line and infusion device (if needed)

● Daily availability of a physician

● Patient and/or family compliance

● Safe environment with access to a telephone, utilities, food, and refrigerator

Specific organisms — There is a role for postexposure chemoprophylaxis to prevent spread of

Neurosurgery — Perioperative antimicrobial prophylaxis is indicated for patients undergoing neurosurgery,

● Basics topic (see "Patient education: Bacterial meningitis (The Basics)")

SUMMARY AND RECOMMENDATIONS

• The dosing for patients with normal renal function is:

- Ceftriaxone – 2 g IV every 12 hours

- Cefotaxime – 2 g IV every four to 6 hours

- Penicillin G – 4 million units IV every 4 hours

- Ampicillin – 2 g IV every 4 hours

● For the initial therapy of N. meningitidis, we recommend a third-generation cephalosporin, such as

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 1283 Version 29.0

Recommendations for empiric antimicrobial therapy for purulent meningitis based

1 to 23 months Streptococcus pneumoniae, Neisseria Vancomycin plus a third-generation

2 to 50 years N. meningitidis, S. pneumoniae Vancomycin plus a third-generation

>50 years S. pneumoniae, N. meningitidis, L. Vancomycin plus ampicillin plus a third-

Penetrating trauma Staphylococcus aureus, coagulase-negative Vancomycin plus cefepime; OR vancomycin

Postneurosurgery Aerobic gram-negative bacilli (including P. Vancomycin plus cefepime; OR vancomycin

Immunocompromised S. pneumoniae, N. meningitidis, L. Vancomycin plus ampicillin plus cefepime; OR

Graphic 71968 Version 5.0

Recommended intravenous dosages of antimicrobial therapy for adults with

Antimicrobial agent Dose (adult)

Amikacin 5 mg/kg every 8 hours*

Ampicillin 2 g every 4 hours

Aztreonam 2 g every 6 to 8 hours

Cefepime 2 g every 8 hours

Cefotaxime 2 g every 4 to 6 hours

Ceftazidime 2 g every 8 hours

Ceftriaxone 2 g every 12 hours

Chloramphenicol 1 to 1.5 g every 6 hours ¶

Ciprofloxacin 400 mg every 8 to 12 hours

Gentamicin 1.7 mg/kg every 8 hours*

Meropenem 2 g every 8 hours

Moxifloxacin 400 mg every 24 hours Δ

Nafcillin 2 g IV every 4 hours

Oxacillin 2 g IV every 4 hours

Penicillin G potassium 4 million units every 4 hours

Rifampin 600 mg every 24 hours ◊

Tobramycin 1.7 mg/kg every 8 hours*

Trimethoprim-sulfamethoxazole (cotrimoxazole) 5 mg/kg every 6 to 12 hours § ¥

Vancomycin 15 to 20 mg/kg every 8 to 12 hours ‡

IV: intravenously; MRSA: methicillin-resistant Staphylococcus aureus.

Graphic 60707 Version 13.0